Abstract |
The efficacy of RNA interference (RNAi)-based cancer gene therapy is limited by its unexpected side effects, thus necessitating a strategy to precisely trigger conditional gene knockdown. In this study, we engineered a novel photoactivatable RNAi system, named as polyetherimide-modified single-wall carbon nanotube (PEI-SWNT)/pHSP-shT, that enables optogenetic control of targeted gene suppression in tumor cells. PEI-SWNT/pHSP-shT comprises a stimulus-responsive nanocarrier (PEI-SWNT), and an Hsp70B'-promoter-driven RNAi vector (pHSP-shT). In response to near-infrared (NIR) light irradiation, heating of PEI-SWNT in breast MCF-7 cells triggered gene knockdown targeting human telomerase reverse transcriptase through RNAi, with the gene-knockdown activity capable of being switched off by extinguishing the NIR. Furthermore, we demonstrated that the photoactivatable RNAi system exhibited higher antitumor activity by combining gene therapy and photothermal therapy, both in vitro and in vivo. Optogenetic control of RNAi based on an NIR-activated nanocarrier will potentially facilitate improved understanding of molecular-targeted gene therapy in human malignant tumors.
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Authors | Xueling Ren, Jing Lin, Xuefang Wang, Xiao Liu, Erjuan Meng, Rui Zhang, Yanxiao Sang, Zhenzhong Zhang |
Journal | International journal of nanomedicine
(Int J Nanomedicine)
Vol. 12
Pg. 7885-7896
( 2017)
ISSN: 1178-2013 [Electronic] New Zealand |
PMID | 29138556
(Publication Type: Journal Article)
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Chemical References |
- HSP70 Heat-Shock Proteins
- HSPA7 protein, human
- Nanotubes, Carbon
- Polymers
- polyetherimide
- TERT protein, human
- Telomerase
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Topics |
- Animals
- Female
- Genetic Therapy
(methods)
- HSP70 Heat-Shock Proteins
(genetics)
- Humans
- Infrared Rays
- MCF-7 Cells
- Mice, Inbred BALB C
- Nanotubes, Carbon
(chemistry)
- Phototherapy
(methods)
- Polymers
(chemistry)
- Promoter Regions, Genetic
- RNA Interference
- Spectroscopy, Fourier Transform Infrared
- Telomerase
(genetics)
- Xenograft Model Antitumor Assays
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